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Review
. 2015 Apr;40(4):233-42.
doi: 10.1016/j.tibs.2015.02.006. Epub 2015 Mar 13.

SUMO-mediated regulation of DNA damage repair and responses

Prabha Sarangi  1 , Xiaolan Zhao  2
Affiliations
Review

SUMO-mediated regulation of DNA damage repair and responses

Prabha Sarangi et al. Trends Biochem Sci. 2015 Apr.

Erratum in

  • Trends Biochem Sci. 2015 Jun;40(6):338

Abstract

Sumoylation has important roles during DNA damage repair and responses. Recent broad-scope and substrate-based studies have shed light on the regulation and significance of sumoylation during these processes. An emerging paradigm is that sumoylation of many DNA metabolism proteins is controlled by DNA engagement. Such 'on-site modification' can explain low substrate modification levels and has important implications in sumoylation mechanisms and effects. New studies also suggest that sumoylation can regulate a process through an ensemble effect or via major substrates. Additionally, we describe new trends in the functional effects of sumoylation, such as bi-directional changes in biomolecule binding and multilevel coordination with other modifications. These emerging themes and models will stimulate our thinking and research in sumoylation and genome maintenance.

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Figures

Figure 1
Figure 1. The dynamic SUMO cycle
The maturation, activation, conjugation and deconjugation of the SUMO moiety (shown in 3D structure rendering) are depicted. SUMO enzymes are colored pink, and the substrate is in blue.
Figure 2
Figure 2. Possible mechanisms of on-site sumoylation
Three models are drawn. Note that they can occur independently or sequentially, and only the latter is depicted for simplicity. Substrates (blue, circle) can undergo conformational changes upon binding to DNA lesions, as reflected by the change in the shape of the blue symbol, which may promote sumoylation via the proposed “DNA priming” model ➀. Alternatively or additionally, DNA lesion binding may bring substrates in close proximity with sumoylation enzymes (pink oval). This mechanism, namely “enzyme-substrate proximity” ➁, can function together with the DNA priming mechanism to promote substrate sumoylation at lesion sites, as indicated by the blue symbol with the miniature of SUMO structure on it. Sumoylation of proteins can lead to various effects, two of which are drawn here, namely DNA dissociation (left) or ubiquitin-dependent degradation (right). In the former case, the dissociated protein can be quickly desumoylated to allow recycling of the protein. By associating with DNA or repair substrates, the protein may be protected from desumoylation in a model called “DNA-based shielding” ➂.
Figure 3
Figure 3. Two models for SUMO-based regulation of DNA metabolism functions
SUMO is depicted as its 3D structure rendering. Blue ovals represent substrates. The magnitude of the effects of sumoylation is reflected by the sizes of ovals and the thickness of the arrow underneath them. The ensemble effect model (left) suggests that sumoylation of each substrate has moderate effects, which collectively lead to strong biological consequences. The star effect model (right) suggests that sumoylation of key substrate(s) has strong biological effects, while that of others does not produce any effect. We note that these models are depicted to reflect extreme scenarios for the ease of discussion; intermediate situations can occur as well (not shown).
Figure 4
Figure 4. A few examples of the diverse functional effects of SUMO on DNA metabolism proteins
SUMO-SIM (SUMO-interacting motif) binding promotes group interactions amongst proteins acting in the same pathway by multivalent interaction (protein group glue, A). Sumoylation can also promote dispersal from multimers (anti-glue, B), or a dynamic switch in protein interactions (C). In addition, SUMO can enhance either dissociation from DNA (D) or protein association with DNA (E, adapted from the study on Yku70 [34]). SUMO is depicted as an oval marked S.
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